Raskatov, Jevgenij A. and Virgil, Scott and Lee, Hsiau-Wei and Henling, Lawrence M. and Chan, Ka and Kuhn, Ariel J. and Foley, Alejandro R. (2019) A Facile Method for Separation of the Cryptic Methionine Sulfoxide Diastereomers, Structural Assignment and DFT Analysis. Chemistry: a European Journal . ISSN 0947-6539. (In Press) https://resolver.caltech.edu/CaltechAUTHORS:20200103-100613520
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Abstract
Methionine (Met) oxidation is an important biological redox node, with hundreds if not thousands of protein targets. The process yields methionine oxide (MetO). It renders the sulfur chiral, producing two distinct, diastereomerically related products. Despite the biological significance of Met oxidation, a reliable protocol to separate the resultant MetO diastereomers is currently lacking. This hampers our ability to make peptides and proteins that contain stereochemically defined MetO to then study their structural and functional properties. We have developed a facile method that uses supercritical CO₂ chromatography and allows obtaining both diastereomers in purities exceeding 99%. ¹H NMR spectra were correlated with X‐ray structural information. The stereochemical interconversion barrier at sulfur was calculated as 45.2 kcal/mol, highlighting the remarkable stereochemical stability of MetO sulfur chirality. Our protocol should open the road to synthesis and study of a wide variety of stereochemically defined MetO‐containing proteins and peptides.
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| Additional Information: | © 2019 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim. Accepted manuscript online: 22 December 2019; Manuscript accepted: 20 December 2019; Manuscript revised: 18 December 2019; Manuscript received: 24 October 2019. JAR thanks UCSC for flexible start-up funds and a special research grant to study methionine oxidation. Dr. Indranil Chakraborty is gratefully acknowledged for assistance at early stages of the project. We also thank the late Mr. Stephen Hauskins and the UCSC computing team for help and support. | ||||||
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| Subject Keywords: | Amino Acids; Super-critical CO2 separation; Structural assignment; Sulfur chirality | ||||||
| Record Number: | CaltechAUTHORS:20200103-100613520 | ||||||
| Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20200103-100613520 | ||||||
| Official Citation: | Raskatov, J., Virgil, S., Lee, H., Henling, L., Chan, K., Kuhn, A. and Foley, A. (2019), A Facile Method for Separation of the Cryptic Methionine Sulfoxide Diastereomers, Structural Assignment and DFT Analysis. Chem. Eur. J.. Accepted Author Manuscript. doi:10.1002/chem.201904848 | ||||||
| Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | ||||||
| ID Code: | 100492 | ||||||
| Collection: | CaltechAUTHORS | ||||||
| Deposited By: | Tony Diaz | ||||||
| Deposited On: | 05 Jan 2020 03:40 | ||||||
| Last Modified: | 05 Jan 2020 03:40 |
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